The northeastern United States is highly vulnerable to emerging infectious diseases and terrorism. With the outbreak of West Nile virus, the World Trade Center tragedy, and subsequent anthrax attacks, Region II has the experience and resolve to mobilize its rich resources in biomedical research to advance the nation's biodefense agenda. Region II institutions will establish a Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Disease Research. This consortium, the Northeast Biodefense Center (NBC), will comprise investigators at more than 25 academic and research institutions in New York, New Jersey, Connecticut, Massachusetts and Puerto Rico. The NBC will have strong links to state, federal and local government agencies and laboratories, as well as biotech and pharmaceutical companies. Major basic and translational research programs will be pursued in six thematic areas: 1) B-Cell Related Prophylaxis and Therapeutics; 2) Bacterial Pathogenesis and Therapeutics; 3) Vaccine Platforms; 4) Viral Pathogenesis and Therapeutics; 5) Smallpox Vaccine: Clinical, Immune, and Viral Outcomes; 6) Pathogen Detection and Diagnostics. These programs will intersect with cores that provide support in Informatics, Proteomics, Protein Expression, Monoclonal Antibodies, Animal Models, as well as Administration. Each research program will integrate and intensify the work of several accomplished investigators and will focus on select agents and toxins including Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, Staphylococcus enterotoxin B, pox viruses, and viruses that cause hemorrhagic fever or encephalitis. Zoonotic diseases will be emphasized due to significance in this region, expertise of NBC members, and access to unique resources such as Plum Island Animal Disease Center and networks of investigators and clinicians in comparative medicine. Streamlined technology transfer procedures will be established to facilitate delivery to industry of vaccines, therapeutics, and diagnostics. The translational arm of the NBC has begun with a study of smallpox vaccination and will develop the region's infrastructure for human vaccine trials. Training programs will be established to promote biodefense research objectives by supporting new investigators, senior investigators, and support personnel. An emergency response plan has been developed to rapidly realign the NBC's activities and provide facilities, including cores and scientific support, to first line responders in the event of a biodefense emergency.